A Metagenomics Approach to Frailty in Patients With Cirrhosis Undergoing a Multifactorial Intervention

The relationship between frailty and gut microbiota has not been previously addressed in patients with cirrhosis. We studied by metagenomic shotgun sequencing the faecal microbiota composition associated with frailty in 29 patients with cirrhosis from a previous study (Román, Hepatol Commun 2024). Frail and prefrail patients were randomised to a multifactorial intervention (home exercise, branched-chain amino acids and a multistrain probiotic) or control for 12 months. We observed a positive correlation between the abundance of Rothia dentocariosa and the Liver frailty index (LFI), and between Bacteroides faecis and gait speed. After the multifactorial intervention, LFI improved and the main changes in the microbiota composition were a decrease in the abundance of Akkermansia muciniphila, and an increase in Streptococcus thermophilus, Lactobacillus acidophilus and several species of Bifidobacterium. We conclude that frailty in patients with cirrhosis was associated with a distinct microbiome signature. After a long-term multifactorial intervention, frailty improved in parallel with changes in microbiome composition. Trial Registration: ClinicalTrials.gov identifier: NCT04243148.